DESCRIPTION (provided by applicant: Sensory representations are dynamically maintained by ascending and descending connections linking the cerebral cortex and the thalamus. Although the overall extent and topographic specificity of descending corticothalamic projections can equal or surpass that of thalamocortical projections, little is known about their role in perception or learning. Here, we propose a new chemical-genetic approach known as DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to parse the functional contribution of corticothalamic circuits that arise from layer 5 versus layer 6 of primay and secondary areas of the auditory cortex. By silencing specific cortical feedback circuits while recording from ensembles of thalamic neurons in mice that are either passively listening to sound or are actively engaged in listening tasks, we will gain deeper insight into the workings of multiple, parallel feedback systems that enable the cerebral cortex to modify its afferent input stream.